Drug-Eluting Intraocular Lenses

Notable advances in materials science and in surgical techniques make the management of cataract by replacement of the opaque crystalline with an intraocular lens (IOL), one of the most cost-effective interventions in current healthcare. The usefulness and safety of IOLs can be enhanced if they are endowed with the ability to load and to sustain drug release in the implantation site. Drug-eluting IOLs can prevent infections and untoward reactions of eye tissues (which lead to opacification) and also can act as drug depots for treatment of several other ocular pathologies. Such a myriad of therapeutic possibilities has prompted the design of drug-IOL combination products. Several approaches are under study, namely combination of the IOL with an insert in a single device, soaking in drug solutions, impregnation using supercritical fluids, coating with drug/polymer layers, and covalent grafting of the drug. The advantages/limitations of each technique are discussed in the present review on selected examples. Although more in vivo data are required, the information already available proves the interest of some approaches in ocular therapeutics.     

合理看待药物洗脱支架晚期血栓问题

冠状动脉支架现广泛应用于冠心病的介入治疗中。支架内血栓是金属裸支架和药物洗脱支架的一个并发症,可导致心肌梗死或死亡。最近,药物洗脱支架引起晚期支架内血栓的问题引起人们的广泛关注。支架血栓的危险因素包括操作因素(如支架贴壁不良、置入支架的数目、支架长度及夹层)、患者及病变因素、过早停用抗血小板药物以及支架释放的药物使内皮延迟愈合等。现对支架晚期血栓的概念、发生的危险因素、防治措施等进行探讨。     

第二代药物洗脱支架

自2002年药物洗脱支架被引入以来,该类支架已经在冠状动脉介入治疗中获广泛应用。药物洗脱支架就是在金属裸支架的表面涂以包含抗增殖剂的聚合物。这种聚合物能在支架置入后的数周至数月内持续释放并持续抑制血管内膜增生。第一代药物洗脱支架主要是西罗莫司和紫杉醇支架,相对于金属裸支架和单纯球囊扩张,它在减少支架内再狭窄和再次介入方面显示了优势。     

Drug-Eluting Stents, Restenosis and Revascularization

Several meta-analyses have demonstrated the superiority of drug-eluting stents (DES) in reducing the incidence of restenosis, target vessel revascularization and target lesion revascularization compared to their predecessor, the bare-metal stent. In comparing Cypher and Taxus stents, the two most recent meta-analyses have given the edge to the Cypher. However, it must be stressed that the superiority of one DES over another remains debatable due to ever changing "real-world data" compared to those attained from randomized trials. The newer sirolimus analogs and selective inhibitors are challenging the old guard in their quest to further limit restenosis. So too are the newer "high-tech" polymers and additionally by using more biodegradable material in the stent's design. Stents aimed at targeting lesions are a new armament in the battle against restenosis and together with combination therapies are exciting key areas to watch. The ideal way to treat a DES in-stent restenosis is still a challenge and hence the impetus is to avoid it from happening in the first place.     

Vascular Pathology of Drug-Eluting Stents

Polymer-based sirolimus- (Cypher) and paclitaxel-eluting stents (Taxus), so-called drug-eluting stents (DES), have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary revascularization (PCI). While these stents have reduced rates of restenosis and late lumen loss compared to bare-metal stents (BMS), late thrombosis, a life-threatening complication of this technology, has emerged as a major concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that the DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared to BMS. This so-called delayed healing is "identified as" the primary substrate of an underlying cause of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis include penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions. These represent additional barriers to healing and should be avoided if DES are to be used in order to minimize the late thrombotic risks of these devices. Since the time course of complete healing with DES is unknown, the optimal duration of antiplatelet treatment remains to be determined.     

Future Directions of Drug-Eluting Stents

Coronary artery stents have changed the face of interventional cardiology since their introduction in 1986. The commercial release of drug-eluting stents in 2002 promised to abolish in-stent restenosis as the predominant clinical limitation following stent implantation. Concerns raised about increased risks of adverse events with drug-eluting stents now appear unfounded but have heralded a new era of research, where only hard clinical end-points in sufficiently large numbers of patients are considered adequate. In this review, we highlight some of the potential future directions of drug-eluting stents including specialized stent platforms (including dedicated bifurcation stents), fully degradable stents, and the potential use of stents to prevent cardiac events.     

药物支架晚期血栓

药物支架很大程度上解决了支架内再狭窄的问题。但最近药物支架晚期血栓的问题倍受关注。现就可能导致药物支架晚期血栓的因素及支架的发展前景做一简要综述。     

Drug-Eluting Stents in the Elderly

The introduction of drug-eluting stents (DES) in 2003 has had a great impact on the management of coronary artery disease in the United States. The application of DES to older adults, the population with the highest prevalence of and worst prognosis for coronary artery disease, remains relatively more controversial. Dual-antiplatelet therapy, which is recommended for at least 12 months after DES placement, is particularly problematic for older patients because of greater age-related bleeding risks. Unfortunately, few current data are available to gauge the balance of risk and benefit in elderly community-dwelling DES patients. Although trial data show a benefit for DES among elderly patients, many older adults typically are excluded from randomized trials because of comorbidities, making generalizability of DES safety based on trial data less certain. New, more potent thienopyridines may place the elderly at a particularly elevated bleeding risk. There is a fine balance between efficacy and safety for older DES patients that still needs to be clarified. As the population ages, these issues become more pervasive and of widespread concern. This review summarizes the current literature on DES therapy in the elderly, with a focus on effectiveness and safety profiles of DES versus bare metal stents.     

药物洗脱支架置入后再狭窄

尽管药物涂层支架较金属裸支架可以明显降低再狭窄率,但随着临床中的广泛应用,药物支架术后亦有10%发生支架内再狭窄,具体机制不明,主要与介入手术操作和涂层药物、支架本身等有关,多发生支架内局限性狭窄,亦有弥漫病变,最佳治疗手段尚存在争议,再次药物支架置入及血管内放射治疗等都是不错的选择。     

Angioscopic Findings after Drug-Eluting Stent Implantation

In-stent restenosis is the Achilles' heel of standard or bare-metal stent (BMS) implantation, occurring in 10-40% of the patients. Drug-eluting stent (DES) are supposed to inhibit inflammation and neointimal growth and, subsequently, in-stent restenosis. The neointimal proliferation inside the stent is recognized as lumen late loss on angiograms or as an obstruction area (or volume) on intravascular ultrasound (IVUS) in chronic phase. Coronary angioscopy provides direct visualization of the lumen and is capable of macroscopic pathologic diagnosis of atherosclerotic plaques and intracoronary thrombi. This modality is also able to supply detailed information on stent coverage with neointimal hyperplasia. The neointimal growth inside the stent is evaluated as white neointimal coverage over the stent struts. Angioscopic view inside the DES is quite different from that inside the BMS. In this article, the difference in angioscopic findings between the DES and the BMS is shown.     

药物支架的不良反应及临床应用局限性

药物支架主要包括雷帕霉素洗脱支架和紫杉醇洗脱支架两大类,作用机制均为通过抑制平滑肌细胞的增殖来防止再狭窄的形成,由于其对细胞增殖的抑制作用为非选择性,可能影响内皮细胞的再生和内皮层的修复,因此存在一系列不良反应及临床应用局限性。